Effects of Cholesterol and Nuclear Hormone Receptor Agonists on the Production of Transforming Growth Factor-β in Macrophages.

We studied the effects of cholesterol, its oxidized derivatives mevalonate, and nuclear receptor agonists LXR, RXR, and FXR on the production of transforming growth factor-β1 (TGF- β1) by macrophages. After recruiting of macrophage monocytes into the focus of inflammation, the production of TGF-β1 increased by 3.5 times in comparison with control macrophages. Cholesterol diet stimulated the production of TGF-β1 by 2.5 times. Cholesterol directly stimulated macrophage production of TGF-β1 in vitro, while addition of mevalonate to the incubation medium effectively reduced this induced production. Agonists of nuclear receptor sharply reduced the production of TGF-β1 in recruited macrophages. Under conditions of inflammation, hypercholesterolemia can be a factor of fibrogenesis due to TGF-β1 induction in macrophages, which depends on the products of mevalonate biochemical chain. [ABSTRACT FROM AUTHOR]